Nerve cuff with pocket for leadless stimulator

ABSTRACT

An extravascular nerve cuff that is configured to hold a leadless, integral, implantable micro stimulator. The nerve cuff may include a cuff body having a pocket or pouch for removably receiving the implantable device within. The nerve cuff can be secured around the nerve such that the electrodes of the device are stably positioned relative to the nerve. Furthermore, the nerve cuff drives the majority of the current from the stimulation device into the nerve, while shielding surrounding tissues from unwanted stimulation.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.16/292,144, filed on Mar. 4, 2019, titled “NERVE CUFF WITH POCKET FORLEADLESS STIMULATOR,” now U.S. Patent Application Publication No.2019/0192847, which is a continuation of U.S. patent application Ser.No. 15/645,996, filed Jul. 10, 2017, titled “NERVE CUFF WITH POCKET FORLEADLESS STIMULATOR,” now U.S. Pat. No. 10,220,203, which is acontinuation of U.S. patent application Ser. No. 14/931,711, filed Nov.3, 2015, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR,” nowU.S. Pat. No. 9,700,716, which is a continuation of U.S. patentapplication Ser. No. 14/536,461, filed Nov. 7, 2014, titled “NERVE CUFFWITH POCKET FOR LEADLESS STIMULATOR,” now U.S. Pat. No. 9,174,041, whichis a divisional of U.S. patent application Ser. No. 12/797,452, filedJun. 9, 2010, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR,now U.S. Pat. No. 8,886,339, which claims the benefit under 35 U.S.C. §119 of U.S. Provisional Patent Application No. 61/185,494, filed on Jun.9, 2009, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR,” eachof which is herein incorporated by reference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

FIELD OF THE INVENTION

The present invention relates generally to implantable neuralstimulators, and more specifically to a nerve cuff with a pocket forremovably receiving an active leadless stimulation device, and methodsof stimulating a nerve using such nerve cuff.

BACKGROUND OF THE INVENTION

Implantable electrical stimulation devices have been developed fortherapeutic treatment of a wide variety of diseases and disorders. Forexample, implantable cardioverter defibrillators (ICDs) have been usedin the treatment of various cardiac conditions. Spinal cord stimulators(SCS), or dorsal column stimulators (DCS), have been used in thetreatment of chronic pain disorders including failed back syndrome,complex regional pain syndrome, and peripheral neuropathy. Peripheralnerve stimulation (PNS) systems have been used in the treatment ofchronic pain syndromes and other diseases and disorders. Functionalelectrical stimulation (FES) systems have been used to restore somefunctionality to otherwise paralyzed extremities in spinal cord injurypatients.

Typical implantable electrical stimulation systems can include a systemwith one or more programmable electrodes on a lead that are connected toan implantable pulse generator (IPG) that contains a power source andstimulation circuitry. However, these systems can be difficult and/ortime consuming to implant, as the electrodes and the IPG are usuallyimplanted in separate areas and therefore the lead must be tunneledthrough body tissue to connect the IPG to the electrodes. Also, leadsare susceptible to mechanical damage over time as they are typicallythin and long.

Recently, small implantable neural stimulator technology, i.e.microstimulators, having integral electrodes attached to the body of astimulator has been developed to address the disadvantages describedabove. This technology allows the typical IPG, lead and electrodesdescribed above to be replaced with a single device. Elimination of thelead has several advantages including reduction of surgery time byeliminating, for example, the need for implanting the electrodes and IPGin separate places, the need for a device pocket, tunneling to theelectrode site, and strain relief ties on the lead itself. Reliabilityis therefore increased significantly, especially in soft tissue andacross joints because active components, such as lead wires, are nowpart of the rigid structure and are not subject to the mechanical damagedue to repeated bending or flexing over time.

However, the leadless integral devices tend to be larger and moremassive than the electrode/lead assemblies, making it difficult tostably position the device in the proper position in respect to a nerve.Without device stability, the nerve and/or surrounding muscle or tissuecan be damaged due to movement of the assembly.

There remains a need for a leadless integral device that is stablypositioned on the nerve, and can provide for removal and/or replacementof the stimulation device with relative ease.

SUMMARY OF THE INVENTION

Described herein are extravascular nerve cuffs for securing a leadless,integral, implantable device to a nerve. The nerve cuff typicallyincludes a pouch or pocket. The cuff electrode configuration of thestimulation device allows the device to be stably positioned proximate anerve, such as the vagus nerve. Furthermore, the cuff electrodeconfiguration also has the characteristics of driving most of thecurrent into the nerve, while shielding surrounding tissues fromunwanted stimulation. Methods of securing a leadless microstimulatorusing such nerve cuffs are also described herein, as well as methods ofstimulating a nerve using microstimulators secured using such cuffs.

There are numerous advantages to using leadless cuffs with amicrostimulator, including a decrease in encapsulation (e.g., to about100 microns) compared to systems without leadless cuffs, since there isless “tugging” on the leadless cuff. Furthermore, leadless cuffs, whichmay securely attach to a nerve and hold a microstimulator in position,may allow a microstimulator to be modified or replaced while maintainingthe same positioning relative to the nerve.

In one embodiment of the invention, the nerve cuff generally includes acuff body or carrier, made of a flexible material such as amedical-grade soft polymeric material (e.g., Silastic™ or Tecothane™)forming a cuff or sleeve, having a pocket or pouch defined therein forremovably receiving a leadless stimulation device. The leadlessstimulation device is positioned within the pocket or sleeve such thatthe electrodes of the device are positioned proximate the nerve to bestimulated. The pocket can be defined by the space between thestimulation device and an inner surface of the cuff body or can comprisea pouch-like structure attached to the cuff body for containing thestimulation device. The nerve cuff can be coupled to the nerve, asurrounding sheath that contains the nerve, or both depending on thedesired level of stability.

The nerve cuff can be implanted by first dissecting the nerve, such asthe vagus nerve, from its surrounding sheath, wrapping the nerve cuffaround the nerve, coupling or suturing the nerve cuff to one of eitherthe nerve or the sheath and inserting the stimulation device within thepocket or pouch of the cuff body such that the stimulation device isproximate the nerve.

For example, described herein are nerve cuffs for securing a leadlessmicrostimulator in stable communication with a nerve. A nerve cuff mayinclude: a cuff body having a channel extending within the length of thecuff body for passage of a nerve; a pocket within the cuff body,configured to removably hold the leadless microstimulator; and anelongate opening slit extending the length of the cuff body configuredto be opened to provide access to the pocket.

The nerve cuff may also include an internal electrical contact withinthe cuff body. For example, the internal electrical contact may beconfigured to electrically couple the microstimulator and the nerve. Insome variations, the nerve further includes an external electricalcontact on the outer surface of the cuff body configured to couple withthe microstimulator.

In some variations, the cuff body comprises shielding configured toelectrically isolate the microstimulator within the nerve cuff. The cuffbody may be of uniform thickness, or it may have a non-uniformthickness. For example, the cuff body may have a thickness between about5 and about 20 mils.

In some variations, the outer surface of the nerve cuff is substantiallysmooth and atraumatic. The nerve outer surface of the nerve cuff may berounded and/or conforming. For example, the body may conform to theregion of the body into which the cuff and/or microstimulator areimplanted.

In some variations, the channel comprises a support channel configuredto support the nerve within therein, to prevent pinching of the nerve.

The elongate opening slit may extend the length of the cuff body in aninterlocking pattern. In some variations, the slit extends along theside of the cuff body, adjacent to the channel. In other variations, theslit extends along the top of the cuff body, opposite to the channel.

The nerve cuff may also include one or more attachment sites in theelongate opening slit configured to help secure the slit closed. Forexample, the attachment sites may be holes or passages for a suture.

In some variations, the cuff body is formed of a flexible andbiocompatible polymer (e.g., a polymeric biocompatible material such asa silicone polymer.

Also described herein are nerve cuffs for securing a leadlessmicrostimulator in stable communication with a nerve, comprising: aninsulating cuff body having a nerve channel extending within the lengthof the cuff body for passage of a nerve, wherein the cuff bodyelectrically isolates the microstimulator within the cuff body; aconductive surface within the nerve channel configured to engage one ormore electrical contacts on the microstimulator; a pocket within thecuff body, configured to removably hold the leadless microstimulator;and an elongate opening slit extending the length of the cuff bodyconfigured to be opened to provide access to the pocket.

As mentioned above, the nerve cuff may include one or more externalelectrical contact on the outer surface of the cuff body configured tocouple with the micro stimulator.

In some variations, the nerve cuff body has a uniform thickness; inother variations, the nerve cuff body has a non-uniform thickness. Thecuff body may have a thickness between about 5 and about 20 mils.

The outer surface of the nerve cuff may be substantially smooth andatraumatic. For example, the outer surface of the nerve cuff may becontoured.

In some variations, channel through the nerve cuff comprises a supportchannel configured to support the nerve within therein, to preventpinching of the nerve.

In some variations, the elongate opening slit extends the length of thecuff body in an interlocking pattern. For example, the interlockingpattern may be a zig-zag pattern, or a sinusoidal pattern.

Also described herein are methods of implanting a leadlessmicrostimulator in communication with a vagus nerve, the methodcomprising: exposing a vagus nerve; opening a slit of a nerve cuffhaving a nerve cuff body, wherein the slit opens along the length of thenerve cuff body; placing the nerve cuff around the vagus nerve so thatthe nerve is within a channel extending the length of nerve cuff;inserting a leadless microstimulator within a pocket in the nerve cuff;and securing the slit of the nerve cuff closed so that the leadlessmicrostimulator is in electrical communication with the nerve andelectrically isolated within the nerve cuff body.

In some variations, the step of securing the opening slit of the nervecuff closed comprises securing the slit so that the leadlessmicrostimulator engages an internal electrical contact within the nervecuff body. The leadless microstimulator may engage an internalelectrical contact configured to provide circumferential stimulationaround the nerve within the channel.

The step of securing may comprise suturing the slit closed. In somevariations, the slit may be self-closing. For example, there may beenough tension in the cuff to keep it closed by itself. In somevariations, dissolvable sutures may be used to keep it closed until thebody encapsulates it.

The method may also include the step of testing the microstimulator toconfirm electrical communication with the nerve.

In some variations, the step of placing the nerve cuff comprises placingan oversized nerve cuff around the vagus nerve.

Also described herein are methods of implanting a leadlessmicrostimulator in communication with a vagus nerve including the stepsof: exposing a vagus nerve; opening a slit of a nerve cuff having anerve cuff body, wherein the slit opens along the length of the nervecuff body; placing the nerve cuff around the vagus nerve so that thenerve is within a channel extending the length of nerve cuff; insertinga leadless microstimulator within a pocket in the nerve cuff so that themicrostimulator communicates with one or more internal electricalcontacts within the nerve cuff; and closing the slit of the nerve cuffso that the nerve is in electrical communication with the one or moreinternal electrical contact.

In some variations, the leadless microstimulator and the internalelectrical contact is configured to provide circumferential stimulationaround the nerve within the channel. The step of closing may include thestep of securing the slit of the nerve cuff closed. For example, thestep of closing may comprise suturing the slit closed. The step ofplacing the nerve cuff may comprise placing an oversized nerve cuffaround the vagus nerve.

The above summary of the invention is not intended to describe eachillustrated embodiment or every implementation of the present invention.The figures and the detailed description that follow more particularlyexemplify these embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view depicting a nerve cuff with stimulationdevice implanted proximate a nerve, according to an embodiment of theinvention.

FIG. 1A is a top view depicting the implanted nerve cuff withstimulation device of FIG. 1;

FIG. 1B is a top view depicting the implanted nerve cuff withstimulation device according to an alternative embodiment of theinvention;

FIG. 2 is a front view depicting an implanted nerve cuff with strainrelief according to an embodiment of the invention;

FIG. 3 is a front view depicting an implanted nerve cuff with sutureholes according to an embodiment of the invention;

FIG. 4 is an open view depicting the nerve cuff with suture holes ofFIG. 3;

FIG. 5 is a top view depicting a closing device for the implanted nervecuff of FIG. 1;

FIG. 6 is a perspective view depicting marsupializaton of thestimulation device within a pocket of the nerve cuff of FIG. 1;

FIG. 7A is a top view depicting a nerve cuff having a conforming shieldaccording to an embodiment of the invention.

FIG. 7B is a front view of the nerve cuff of FIG. 7a .

FIG. 8A is a top view depicting an open nerve cuff according to anembodiment of the invention;

FIG. 8B is a front view of the nerve cuff of FIG. 8a ; and

FIG. 8C is a top view depicting the nerve cuff of FIG. 8 in a closedconfiguration.

FIGS. 9A and 9B show side views through a section of the cuff body wall,indicating uniform and varying thicknesses, respectively.

FIGS. 10A-10D illustrate one variation of a nerve cuff as describedherein. FIG. 10A shows an end view, FIG. 10B is a side perspective view,FIG. 10C is a side view, and FIG. 10D is a longitudinal section throughthe device attached to a nerve, showing internal features including amicro stimulator.

FIGS. 11A-11D illustrate another variation of a nerve cuff. FIG. 11Ashows an end view, FIG. 11B is a side perspective view, FIG. 11C is aside view, and FIG. 11D is a longitudinal section through the deviceattached to a nerve, showing internal features including amicrostimulator.

FIG. 12 shows one variation of a microstimulator that may be used in thenerve cuffs described herein.

FIG. 13A shows a perspective view of another variation of amicrostimulator that may be used as described herein. FIGS. 13B and 13Care end and bottom views, respectively, of the microstimulator shown inFIG. 13A.

FIGS. 14A and 14B illustrate side and end views, respectively of anothervariation of a nerve cuff.

FIGS. 15A-15C show top, side and sectional views, respectively of anerve cuff such as the one shown in FIG. 14A, attached to a nerve. FIG.15D is a section though the middle of a nerve cuff with amicrostimulator secured there.

FIG. 16 is an internal end view of a microstimulator similar to the onesshown in FIGS. 14A-15D.

FIG. 17 is a sectional view showing the inside of another variation of anerve cuff.

FIG. 18 is a side perspective view of the top-opening nerve cuff shownin FIG. 17.

FIG. 19 is a side perspective view of a side-opening nerve cuff.

FIG. 20 is a transparent view of the bottom of a nerve cuff, showing thenerve channel.

FIG. 21 is a side view of another variation of a nerve cuff.

FIGS. 22A-22H illustrate steps for inserting a nerve cuff such as thenerve cuffs described herein.

FIG. 23 shows an equivalent circuit modeling current loss when the nervecuff is only loosely arranged over the nerve.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail. It should be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the intention is tocover all modifications, equivalents, and alternatives falling withinthe spirit and scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the invention are directed to a retaining device, such asa carrier or cuff, which positions active contacts, i.e. electrodes, ofa stimulation device against the targeted nerve directing the currentfrom the electrodes into the nerve. The retaining device also inhibitsor prevents the current from flowing out to the surrounding tissue.

Referring to FIG. 1, one example of a nerve cuff 100 adapted for holdinga stimulation device is coupled to a nerve 102. Nerve 102 can compriseany nerve in the human body targeted for therapeutic treatment, such as,for example, the vagus nerve. Nerve cuff adapter 100 generally comprisesan outer carrier or cuff 104 body that can comprise any of a variety ofmedical grade materials, such as, for example, Silastic™ brand siliconeelastomers, or Tecothane™ polymer.

In general, a nerve cuff including a cuff 104 body having (or forming) apouch or pocket 106 for removably receiving an active, implantablestimulation device 108 having one or more integrated, leadlesselectrodes 110 on a surface of stimulation device 108 proximate nerve102. As illustrated in FIGS. 1 and 1A, nerve cuff 100 wraps around nerve102 such that electrodes 110 are positioned proximate nerve 102.

Contacts or electrodes 110 can be positioned directly against nerve 102,as illustrated in FIG. 1A, or in close proximity to nerve 102, asillustrated in FIG. 1B. Referring specifically to FIG. 1B, closeproximity of electrodes 110 and nerve 102 will leave a gap or space 112that may naturally be filled with fluid or connective tissue. In oneembodiment of the invention, electrodes 110 and/or the inner surface ofcuff body 104 can include optional steroid coatings to aid in reducingthe local inflammatory response and high impedance tissue formation.

In one embodiment, the pocket 106 for containing the stimulation device108 is defined by the open space between the nerve 102 and the innersurface of the cuff body 104. Stimulation device 108 can be passivelyretained within pocket 106 by the cuff body 104, or can be activelyretained on cuff body with fastening means, such as, for example,sutures. In other embodiments, pocket 106 can comprise a pouch-likestructure attached to cuff body 104 into which stimulation device 108can be inserted. Stimulation device 108 can be passively retained withina pouch-like pocket by simply inserting the device 108 into the pocketor can be actively retained with fastening means. A pouch-like pocketcan be positioned either in the interior or on the exterior of cuff body104. Pouch-like pocket 106 and/or cuff body 104 can include accessopenings to allow electrodes to be positioned directly proximate oradjacent to nerve 102.

Cuff body 104 can have a constant thickness or a varying thickness asdepicted in FIGS. 9A and 9B. The thickness of cuff body 104 can bedetermined to reduce the palpable profile of the device once thestimulation device is inserted. In one embodiment, the thickness of cuffbody can range from about 1 to about 30 mils, or from about 5 to about20 mils. In one embodiment shown in FIG. 9B, cuff 104 can have a greaterthickness at a top and bottom portion of the cuff and a smallerthickness in a middle portion where the stimulation device is contained.

A key obstacle to overcome with implanting stimulation devices proximatenerves or nerve bundles is attaching a rigid structure that makes up thestimulation device along a fragile nerve in soft tissue. In oneembodiment of the invention, this issue is resolved by encasing nerve102 and device 108 in a cuff body 104 that comprises a low durometermaterial (e.g., Silastic™ or Tecothane™) as described above, thatconforms around nerve 102. Further, as illustrated in FIG. 2, cuff body104 can comprise strain reliefs 114 on its ends that reduce or preventextreme torsional rotation and keep nerve 102 from kinking. Strainreliefs 114 can coil around nerve 102, and are trimmable to a desiredsize, such as the size of nerve 102. Further, strain relief 114 can betapered. In some variations, the lateral ends of the nerve cuff, formingthe channel into which the nerve may be place, are tapered and have atapering thickness, providing some amount of support for the nerve. Insome variations, the channel through the nerve cuff in which the nervemay sit, is reinforced to prevent or limit axial loading (e.g.,crushing) of the nerve or associated vascular structures when the nerveis within the cuff.

Given the design or architecture of cuff body 104, any vertical movementof cuff body 104 on nerve 102 is not critical to electrical performance,but can result in friction between device 108 and nerve 102 that couldpotentially damage nerve 102. For that reason, device 108 should readilymove up and down nerve 102 without significant friction while beingsufficiently fixated to nerve 102 so that eventually connective tissuecan form and aid in holding device 108 in place. The challenge isstabilizing device 108 so that it can be further biologically stabilizedby connective tissue within several weeks.

Nerve cuff 100 should not be stabilized to surrounding muscle or fasciathat will shift relative to the nerve. Therefore, referring to FIGS. 3and 4, nerve cuff 100 can further comprise connection devices, such assuture holes or suture tabs, for coupling and stabilizing cuff body 104with device 108 to at least one of the nerve bundle or nerve 102, andthe surrounding sheath that contains nerve 102. In one embodiment of theinvention, for example, as shown in FIG. 3, cuff body 104 can comprisesuture holes 116 that can be used with sutures to couple cuff 104 bodywith device 108 to the surrounding nerve sheath. In an alternativeembodiment of the invention, shown in FIG. 4, suture tabs 118 withsuture holes 116 extend from one or both sides of cuff body 104.

Several stabilizing mechanisms can be used, including suture tabs andholes, staples, ties, surgical adhesives, bands, hook and loopfasteners, and any of a variety of coupling mechanisms. FIGS. 3 and 4,for example, illustrates suture tabs and holes that can be fixed to thesurrounding sheath with either absorbable sutures for soft tissue orsutures demanding rigid fixation.

FIG. 5 illustrates sutures 120 that clamp or secure cuff body 104 withdevice 108 to a surgeon-elected tension. Sutures 120 can be tightened orloosened depending on the level of desired stability and anatomicalconcerns. As shown in FIG. 5, a gap 122 can be present so long as cuffadapter 100 is sufficiently secured to nerve 102, with a limit set to anerve diameter to prevent compression of the vasculature within nerve102. Surgical adhesives (not shown) can be used in combination withsutures 120 on surrounding tissues that move in unison with the neuraltissue.

Muscle movement against cuff adapter 100 can also transfer undesiredstresses on nerve 102. Therefore, in an embodiment of the invention, lowfriction surfaces and/or hydrophilic coatings can be incorporated on oneor more surfaces of cuff body 104 to provide further mechanisms reducingor preventing adjacent tissues from upsetting the stability of nervecuff 100.

FIG. 6 illustrates a nerve cuff 100 with a stimulator device removablyor marsupially secured within pocket or pouch 106 of cuff body 104. Bythe use of recloseable pouch 106, active stimulator device 108 can beremoved or replaced from cuff body 104 without threatening orendangering the surrounding anatomical structures and tissues. Device108 can be secured within cuff body 104 by any of a variety of securingdevices 124, such as, for example, sutures, staples, ties, zippers, hookand loop fasteners, snaps, buttons, and combinations thereof. Sutures124 are shown in FIG. 6. Releasing sutures 124 allows access to pouch106 for removal or replacement of device 108. Not unlike typical cuffstyle leads, a capsule of connective tissue can naturally encapsulatenerve cuff 100 over time. Therefore, it will most likely be necessary topalpate device 108 to locate device 108 and cut through the connectivetissue capsule to access sutures 124 and device. Theremovable/replaceable feature of nerve cuff 100 is advantageous overother cuff style leads because such leads cannot be removed due toentanglement with the target nerve and critical vasculature.

As discussed supra, compression of nerve 102 must be carefullycontrolled. Excess compression on nerve 102 can lead todevascularization and resulting death of the neural tissue. Compressioncan be controlled by over-sizing or rightsizing nerve cuff 100, so thatwhen pocket sutures 124 are maximally tightened, the nerve diameter isnot reduced less that the measured diameter. Cuffs formed from Silastic™or Tecothane™ materials are relatively low cost, and therefore severalsizes can be provided to the surgeon performing the implantation ofnerve cuff 100 to better avoid nerve compression.

Miniature stimulators, such as device, are still large enough to be feltand palpated by patients as are state-of-the-art commercial cuffsystems. Referring to FIG. 7, to avoid such palpation, nerve cuff 100can further comprise a protecting shield 126 conforming to the shape ofthe anatomical structures, such as in the carotid sheath. In thisembodiment, nerve cuff 100 is secured around the vagus nerve, whileisolating device 108 from contact with both the internal jugular vein(IJV) 132, and common carotid artery 134. Shield 126 then furtherisolates device 108 from other surrounding tissues. It is critical tominimize the profile of the entire cuff adapter 100 while maintainingthe compliance of such materials as Silastic™ or Tecothane™. In oneembodiment of the invention, protective shield 126 is formed from a PETmaterial, such as Dacron®, optionally coated with Silastic™ orTecothane™ forming a thin and compliant structure that will allow fortissue separation when required.

When a nerve does not provide sufficient structural strength to supportnerve cuff adapter 100, collateral structures can be included in or oncuff body 104. Because of a high degree of anatomical variance such ascheme must demand the skill of the surgeon to utilize a highlycustomizable solution. FIG. 8a illustrates a variable size nerve cuff100 with a wrappable retainer portion 128 extending from cuff body 104.As shown in FIG. 8c , cuff body 104 is secured around nerve 102, whileretainer portion 128 is secured around the sheath or other surroundinganatomical structures, such as the IJV 132 and/or carotid artery 134. Asshown in FIG. 8b , wrappable retainer portion 128 can include securingdevices 130, such as suture holes, for securing the entire nerve cuff100 around the desired anatomical structures. This configuration allowsfor access to device 108 through pocket 106 as in previous embodiments,while adapting to a multitude of anatomical variations to obtain thedesired stability of nerve cuff 100 on nerve 102.

FIGS. 10A-10D illustrate a variation of a nerve cuff that includes acuff body forming a channel (into which a nerve may be fitted) and anslit formed along the length of the nerve cuff body. In this example,the nerve cuff body also includes a pocket region within the cuff bodypositioned above the nerve channel. The top of the body (opposite fromthe nerve channel) includes a long slit 1003 along its length forming onopening. The cuff body may be along the slit by pulling apart the edges,which may form one or more flaps. In the example shown in FIG. 10A, theslit may be split open to expose the inside of the nerve cuff and allowthe nerve to be positioned within the internal channel, so that the cuffis positioned around the nerve. The same split may be used to insert themicrocontroller as well. In some variations a separate opening (slit orflap) may be used to access the pocket or pouch for the microcontroller.

FIG. 10B shows a perspective view of the nerve cuff holding amicrocontroller after it has been inserted onto a nerve (e.g., the vagusnerve). FIG. 10C shows a side view of the same. FIG. 10D shows a sectionthough the view of FIG. 10C, illustrating then nerve within the channelformed through the nerve cuff, and a microstimulator held snugly withinthe nerve cuff so that the microstimulator is in electricalcommunication with the nerve via a shared surface between the two. Insome variations, as discussed below, the microstimulator is held in aseparate, possibly isolated, compartment and electrical contact with thenerve is made by one or more internal leads that couple themicrostimulator with the nerve through an internal contact.

The exemplary cuff shown in FIGS. 10A-10D has a conformal configuration,in which the wall thickness is relatively constant, as can be seen fromthe sectional view in FIG. 10D. In contrast, FIGS. 11A-11D illustrate avariation of a nerve cuff in which the wall thickness varies along theperimeter. This non-uniform thickness may effectively cushion the devicerelative to the surrounding tissue, even as the patient moves orpalpitates the region. This may have the added benefit of preventingimpingement of the nerve. Similarly, the variable thickness may enablesmooth transitions and help conform the cuff to the surrounding anatomy.

For Example, FIG. 11A shows an end view (with exemplary dimensionsillustrated). It should be noted that in any of the figures or examplesprovided herein, the dimensions shown or described are for illustrationonly. In practice the dimensions may be +/− some percentage of thevalues shown (e.g., +/−5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, etc.). Thesection through the device shown in FIG. 11D illustrates the non-uniformthickness of the walls.

Both nerve cuff variations shown in FIGS. 10A-10D and FIGS. 11A-11D aresubstantially rounded or conforming, and have non-traumatic (oratraumatic) outer surfaces. As mentioned, this relatively smooth outersurface may enhance comfort and limit encapsulation of the nerve cuffwithin the tissue.

As can be seen from FIGS. 10D and 11D, the microstimulator typicallyrests above (in the reference plane of the figure) the length of thenerve when inserted into the nerve cuff. In some variations, themicrostimulator includes a contoured outer surface onto which one ormore contacts (for contacting the nerve or an internal conductor withinthe nerve cuff) are positioned. For example, FIG. 12 illustrates onevariation of a microstimulator 1201. In this example, themicrostimulator includes one or more contacts on its outer surface withwhich to provide stimulation to a nerve. FIG. 13A shows anothervariation of a microstimulator 1301 in which the outer surface (thebottom in FIG. 13A) is curved to help form a channel surrounding thenerve when the microstimulator is inserted into the nerve cuff. FIG. 13Bshows an end view, illustrating the channel concavity 1303 extendingalong the length of the micro stimulator, and FIG. 13C shows a bottomview, looking down onto the channel region. In practice, themicrostimulator shown may be placed within the nerve cuff and be held inposition at least partially around the nerve. Thus, the microstimulatormay help protect the nerve, which may lie within this channel. Asmentioned above, and described in greater detail below, it is notnecessary that the nerve lie against the contacts, as current may beconducted to the nerve from within the nerve cuff, which may beinsulated sufficiently to prevent excessive leak or spillover of thecurrent even when the cuff is oversized and only loosely surrounds thenerve. Furthermore, the nerve cuff may include one or more internalcontacts allowing the current from the microstimulator to be distributedto the nerve via one or more internal contacts or leads, includingcircumferentially around the nerve.

FIGS. 14A and 14B show another variation of a nerve cuff. In thisexample, the slit forming the opening is positioned on the upper surface(opposite to the nerve channel) along the length of the device. The slitis formed in an interlocking pattern. In FIG. 14a , the slit forms azig-zag pattern, although other interlocking patterns may be used. Forexample, a sinusoidal or square-wave pattern may be used. Theinterlocking pattern may distribute the strain of closing the cuffaround the nerve and microstimulator, and may make it easier to closethe cuff once it has been positioned and the microstimulator has beeninserted. FIG. 14B shows an end view of the same cuff shown in FIG. 14A.

FIGS. 15A-15C show a similar cuff to the one shown in FIG. 14A from topand side views, connected to a nerve. In these example, the nerveextends through the internal channel and out the openings (which may beoval shaped, as shown in FIG. 14B) at either end. In FIG. 15C, a sectionthrough the length of the device shows that the microstimulator ispositioned in the pouch (cavity) above the nerve. The microstimulatormay be held in place by the walls of the cuff. A conformingmicrostimulator (such as the one shown in FIG. 13A-13C) may be used, asillustrated in the cross-sectional view shown in FIG. 15D. The contacts1503 of the conforming microstimulator are positioned on the bottom ofthe device.

As mentioned briefly above, in some variations of the nerve cuff, theinner surface of the cuff body includes one or more internal contactsconfigured to couple with the microstimulator held within the pouch, andtransmit any applied energy to the nerve (or receive energy from thenerve) positioned within the channel through the nerve cuff. Theinternal lead may be positioned so that it applies current to theunderside (along the bottom region of the channel), or around the sidesof the nerve as it sits within the channel. In some variations theinternal conductor or lead is configured around the channel so that thenerve may be circumferentially stimulated, optimizing the appliedstimulation. FIG. 17 is a long section though a nerve cuff, showing theinside of the cuff, and illustrates a variation of a nerve cuff havingan internal lead 1703 that may apply stimulation to the underside of thenerve. This internal lead may be formed of any biocompatible conductivematerial, including medals, conductive plastics, or the likes. Theinternal lead may include exposed electrode surfaces 1703 for makingcontact with the nerve. Electrodes may be active contacts, also formedof any appropriate conductive material (e.g., metals, conductivepolymers, braided materials, etc.). In some variations, the internallead is coated or treated to help enhance the transfer of energy betweenthe microstimulator and the nerve. Circumferential stimulation orconduction around the lead may reduce the impedances and assure uniformcross-sectional stimulation of the nerve bundle.

FIG. 19 shows another variation of a nerve cuff as described herein. Inthis example, the nerve cuff includes slit 1903 along one side of thedevice, adjacent to the nerve channel, which can be opened (e.g., bypulling apart the flaps or sides of the cuff) to expose nerve channeland the pocket for the microstimulator.

Many of the nerve cuff variations described herein may be opened andpositioned around the nerve, for example, by splitting them open along aslit or hinge region. The device may be configured so that they havesufficient resiliency to close themselves, or remain closed if the edgesof the slit region are brought together. Thus, the device may have ashape memory property that encourages them to close. In some variations,as already mentioned, it may be useful to hold them closed, at leasttemporarily, once they have been positioned over a nerve and themicrostimulator has been positioned within the pocket. Thus, the devicemay include one or more closure elements. For example, the device mayinclude a suture hole or passage for suturing the device closed. In somevariations the nerve cuff includes a button or other fastener element.In some variations, as illustrated in FIGS. 6 and 18, the device may besutured close with a dissolvable suture. A few weeks or months afterinsertion, the nerve cuff may be encapsulated or engulfed by thesurrounding tissue, and will be held closed by this encapsulation. Thus,the dissolvable sutures merely keep the cuff closed for initialanchoring before biointegration and encapsulation occurs.

Any of the nerve cuffs described herein may also include one or moreexternal leads or contacts facing the outside of the nerve cuff body,which may be used to stimulate tissues outside of the nerve cuff, andnot just the nerve within the channel through the cuff. FIG. 21illustrates one variation of a nerve cuff having external leads. In thisexample, the nerve cuff includes two external contacts 2103 that areconnected (through the wall of the nerve cuff body) to themicrostimulator held within the nerve cuff pocket. Such external leadsmay be used for sensing in addition to (or instead of) stimulation. Forexample, these electrical contacts may be used to sense otherphysiological events such as muscle stimulation and/or cardiac function.These signals can be applied to aid synchronization of target nervestimulation to minimize artifacts of target stimulation. Such signalsmay be too faint for reliable remote sensing, however the position ofthe microstimulator (insulated within the housing of the nerve cuff) mayallow accurate and reliable sensing.

A nerve may sit within a supported channel through the nerve cuff. Asillustrated in FIG. 20, the channel 2003 may be formed having generallysmooth sides, so as to prevent damage to the nerve and associatedtissues. In some variations the nerve channel though the cuff isreinforced to prevent the cuff from pinching the device or fromover-tightening the device when closed over the nerve. Supports may beformed of a different material forming the nerve cuff body, or fromthickened regions of the same material. Although multiple sizes of nervecuff may be used (e.g., small, medium, large), in some variations, anoversized nerve cuff may be used, because the insulated cuff body willprevent leak of current from the microstimulator to surrounding tissues.

In general, the nerve cuff body may be electrically insulating,preventing leakage of charge from the microstimulator during operation.In some variations the nerve cuff includes shielding or insulationsufficient to electrically insulate the microstimulator within the nervecuff body. Shielding material may particularly include electricallyinsulative materials, including polymeric insulators.

It may be shown mathematically using an equivalent circuit of themicrostimulator, as shown in FIG. 23, that the current from amicrostimulator is not appreciably passed out of even a loosely appliednerve cuff. This allows for the use of oversized nerve cuffs, ratherthan requiring rigorous sizing, or risking constricting the nerve.

For example, assuming a nerve with a cross section of N_(area) issurrounded by a column of fluid F_(area) enclosed by the nerve cuff,where contacts on the inside the microstimulator are spaced E_(spacing)apart (center to center) and have a width E_(width) and circle aroundthe column of fluid and nerve E_(degrees), it can be shown that thecurrent will leak out the ends through a distance between the center ofthe electrode and the end of the nerve cuff that is defined by adistance D_(guard).

The electrical model (illustrated in FIG. 23) consists of a currentsource that drives through DC isolation capacitors (C_(iso2) optional),through the capacitance of each electrode (C_(dl1) and C_(dl2)). Fromthe electrodes, the current passes through either path R_(S) orR_(lp1)+R_(b)+R_(lp2). Whereas a portion of the current passing throughR_(s) provides useful work and the current passing throughR_(lp1)+R_(b)+R_(lp2) passes outside of the device and may causeundesirable effects.

If the nerve has a tight fit, then all the current passing through R_(s)would contribute towards stimulation, but only a portion of the currentcan activate the nerve in the case of a loose fit. Based on this model,it can be shown that (assuming that the nerve and fluid columns form anellipse defined by the major and minor axis a and b, and the pulse widthis short and capacitances are large) just the real impedance andefficiency can be estimated.

The electrode surface area is determined to estimate the complex portionof the impedance: F_(area)=π*a_(F)*b_(F) and N_(area)=π*a_(N)*b_(N).

Assuming the impedance of the cuff contained fluid and nerve has asimilar conductance p and electrodes are spaced at E_(spacing) then thereal resistance of the conduction volume is:R_(working)=E_(spacing)*ρ/F_(area), where the wasted resistance thatshould be maximized is calculated by:R_(wasted)=2*D_(guard)*ρ/F_(area)+R_(bulk), where R_(bulk) is defined asthe free field resistance between the two ends of the cuff.

So the efficiency (η) of the real current delivered in the POD isR_(wasted)/(R_(working)+R_(wasted)), and for the case of an undersizednerve assuming the conductivity of tissue and the fluid column is aboutequivalent then the stimulation efficiency is defined asη_(T)=η*N_(area)/F_(area).

Methods of Insertion

In operation, any of the devices described herein may be positionedaround the nerve, and the microstimulator inserted into the nerve cuff,in any appropriate manner. FIGS. 22A-22H illustrate one variation of amethod for applying the nerve cuff around the nerve and inserting amicrostimulator. In this example, the patient is prepared forapplication of the nerve cuff around the vagus nerve to hold amicrostimulator device securely relative to the nerve (FIG. 22A). Anincision is then made in the skin (≈3 cm) along Lange's crease betweenthe Facial Vein and the Omohyoid muscle (FIG. 22B), and theSternocleidomastoid is retracted away to gain access to the carotidsheath (FIG. 22C). The IJV is then reflected and ≤2 cm of the vagus isdissected from the carotid wall.

In some variations, a sizing tool may be used to measure the vagus(e.g., diameter) to select an appropriate microstimulator and cuff(e.g., small, medium, large). In some variations of the method, asdescribed above, an oversized cuff may be used. The nerve cuff is thenplaced under the nerve with the opening into the nerve cuff facing thesurgeon (FIG. 22D), allowing access to the nerve and the pocket forholding the microstimulator. The microstimulator can then be insertedinside cuff (FIG. 22E) while assuring that the microstimulator contactscapture the vagus, or communicate with any internal contacts/leads. Thenerve cuff may then be sutured shut (FIG. 22F). In some variations, themicrostimulator may then be tested (FIG. 22G) to confirm that the deviceis working and coupled to the nerve. For example, a surgical testerdevice, covered in a sterile plastic cover, may be used to activate themicrostimulator and perform system integrity and impedance checks, andshut the microstimulator off. If necessary the procedure may be repeatedto correctly position and connect the microstimulator. Once this iscompleted and verified, the incision may be closed (FIG. 22H).

The invention may be embodied in other specific forms without departingfrom the essential attributes thereof; therefore, the illustratedembodiments should be considered in all respects as illustrative and notrestrictive. The claims provided herein are to ensure adequacy of thepresent application for establishing foreign priority and for no otherpurpose.

What is claimed is:
 1. A method of implanting a vagus nerve stimulatorto treat inflammation, the method comprising: forming a pocket aroundthe vagus nerve; placing a microstimulator at least partially around thevagus nerve and in the pocket so that the microstimulator is free tomove laterally around the nerve and longitudinally over the nerve,wherein the microstimulator comprises one or more integrated leadlesselectrodes; wherein the microstimulator is held within the pocketwithout any rigid connection to the tissue.
 2. The method of claim 1,wherein forming the pocket comprises forming the pocket at the cervicalregion.
 3. The method of claim 1, wherein forming the pocket comprisesinserting a nerve cuff around the vagus nerve so that the nerve passesthrough the nerve cuff, further wherein placing the microstimulatoraround the vagus nerve comprises placing the microstimulator into thenerve cuff with a space around the nerve formed by the nerve cuff. 4.The method of claim 1, wherein placing the microstimulator comprisesplacing the microstimulator so that there is a gap between the one ormore integrated leadless electrodes and the nerve.
 5. The method ofclaim 1, wherein placing the microstimulator comprises placing themicrostimulator in the pocket so that that the microstimulator issecured around the vagus nerve while isolating the microstimulator fromcontact with both an internal jugular vein and common a carotid artery.6. The method of claim 1, further comprising circumferentiallystimulating the nerve using the microstimulator.
 7. The method of claim1, wherein forming a pocket around the vagus comprises retracting awaytissue around the vagus to provide access.
 8. The method of claim 1,further comprising using a surgical tester to verify operation of themicrostimulator.
 9. A method of implanting a vagus nerve stimulator totreat inflammation, the method comprising: forming a pocket around thevagus nerve at a cervical region; placing a microstimulator around thevagus nerve and in the pocket so that the microstimulator is free tomove laterally around the nerve and longitudinally over the nerve,wherein the microstimulator comprises one or more integrated leadlesselectrodes; wherein the microstimulator is passively held within thepocket without any rigid connection to the tissue.
 10. The method ofclaim 9, wherein forming the pocket comprises inserting a nerve cuffaround the vagus nerve so that the nerve passes through the nerve cuff,further wherein placing the microstimulator around the vagus nervecomprises placing the microstimulator into the nerve cuff with a spacearound the nerve formed by the nerve cuff.
 11. The method of claim 9,wherein placing the microstimulator comprises placing themicrostimulator so that there is a gap between the one or moreintegrated leadless electrodes and the nerve.
 12. The method of claim 9,wherein placing the microstimulator comprises placing themicrostimulator in the pocket so that that the microstimulator issecured around the vagus nerve while isolating the microstimulator fromcontact with both an internal jugular vein and common a carotid artery.13. The method of claim 9, further comprising circumferentiallystimulating the nerve using the microstimulator.
 14. The method of claim9, wherein forming a pocket around the vagus comprises retracting awaytissue around the vagus to provide access.
 15. The method of claim 9,further comprising using a surgical tester to verify operation of themicrostimulator.
 16. A method of implanting a vagus nerve stimulator totreat inflammation, the method comprising: forming a pocket around thevagus nerve at a cervical region by retracting tissue away from thevagus nerve to gain access to the carotid sheath; placing amicrostimulator around the vagus nerve and in the pocket so that themicrostimulator is free to move laterally around the nerve andlongitudinally over the nerve, wherein the microstimulator comprises oneor more integrated leadless electrodes; wherein the microstimulator ispassively held within the pocket without any rigid connection to thetissue.
 17. The method of claim 16, wherein forming the pocket comprisesinserting a nerve cuff around the vagus nerve so that the nerve passesthrough the nerve cuff, further wherein placing the microstimulatoraround the vagus nerve comprises placing the microstimulator into thenerve cuff with a space around the nerve formed by the nerve cuff. 18.The method of claim 16, wherein placing the microstimulator comprisesplacing the microstimulator so that there is a gap between the one ormore integrated leadless electrodes and the nerve.
 19. The method ofclaim 16, wherein placing the microstimulator comprises placing themicrostimulator in the pocket so that that the microstimulator issecured around the vagus nerve while isolating the microstimulator fromcontact with both an internal jugular vein and common a carotid artery.20. The method of claim 16, further comprising circumferentiallystimulating the nerve using the microstimulator.